Vulva + vulva cancer

Question 1

What is stage 1
1A
1B

Answer 1

I Tumor confined to the vulva
IA Lesions ≤2 cm in size, confined to the vulva or perineum and with stromal invasion ≤1.0 mm, no nodal metastasis
IB Lesions >2 cm in size or with stromal invasion >1.0 mm, confined to the vulva or perineum, with negative nodes

Question 2

What is stage 2

Answer 2

Tumor of any size with extension to adjacent perineal structures (lower third of urethra, lower third of vagina, anus) with negative nodes

Question 3

What is stage 3
3A1 + 3A2

3B1 + 3B2

3C

Answer 3

III Tumor of any size with or without extension to adjacent perineal structures (lower third of urethra, lower third of vagina, anus) with positive inguinofemoral nodes

IIIA 1. With 1 lymph node metastasis (≥5 mm), or
2. With 1–2 lymph node metastasis(es) (<5 mm)
IIIB 1. With 2 or more lymph node metastases (≥5 mm), or
2. With 3 or more lymph node metastases (<5 mm)
IIIC With positive nodes with extracapsular spread

Question 4

What is stage 4 vulval cancer

4a 1 + 2

4b

Answer 4

Tumor invades other regional (upper 2/3 urethra, upper 2/3 vagina), or distant structures
Tumor invades any of the following:
1. upper urethral and/or vaginal mucosa, bladder mucosa, rectal mucosa, or fixed to pelvic bone, or
2. fixed or ulcerated inguinofemoral lymph nodes

IVB Any distant metastasis including pelvic lymph nodes

Question 5

Histology of vulval cancer

Concerning features

Answer 5

• Infiltrative growth pattern (compared to a pushing pattern) is associated with higher local recurrence
• Fibromyxoid stroma at the invasive edge is associated with poorer outcome
• Lymphovascular space involvement = increased recurrence

Question 6

What Ix are needed for the work up of vulval cancer ?

Answer 6

1. Cervical cytology, and colposcopy of the cervix and vagina, if applicable, due to the association of HPV‐related cancers with other squamous intraepithelial lesions.
2. Full blood count, biochemical profile, liver profile, and HIV testing.
3. Chest X‐ray.
4. CT or MRI scan of the pelvis and groins may be helpful, especially for locally advanced tumors, to detect any enlarged lymph nodes in the groins or pelvis, erosion into underlying bone, or other metastases. In addition, CT or MRI could be useful in further treatment planning.
5. 18F fluorodeoxyglucose (18F‐FDG) positron emission tomography with computed tomography (PET‐CT) can more effectively assess and detect inguinofemoral lymph node involvement compared with CT

Question 7

What affects recurrence?

Answer 7

• aim for tumor free pathological margins of 8mm

• same site
o associated with margins of 8 mm or less
o mean 21 months later
• different vulva site

o Occurred later - 69 month interval
o likely lichen sclerosis related
o often second primary tumors

Question 8

How to manage close margins ?

Answer 8

• Close margins (less then 5 mm) can be given radiotherapy - it is not possible to reexcise
• Can use brachytherapy - take care to avoid necrosis risk

Question 9

Bartholin gland cancers

How common
What types of cancer
What immunochemistry
What is the pathophysiology

How is it managed

Answer 9

• Bartholin gland carcinoma
o rare, unclear what related to HPV
o Transitional, SCC from the duct and adenocarcinomas from the gland itself
o Diffuse and intense p16 expression consistent with HPV
o Tx radical hemovuvectomy + bilateral groin dissection - difficult to achieve margins and post op radiation may decrease recurrence
o Adenoid cystic lesions radical WLE is adequate and adjuctive RT if positive margins or perineural invasion

Question 10

Malignant melanoma of the vulva
How to stage?
How common
How to Ix

Answer 10

• Second most common
• 10% vulval cancers
• All pigmented lesion should be biopsied, most involve the clitoris or labia minora, de novo or from existing naevus, Irregular, pigmented, recent change, c/o lump or bleeding
• Need to use the Clark or Breslow modification of the staging system not FIGO staging

Question 11

What is the management of vulva malignant melanomas

Answer 11

Surgery is Tx of choice - radical wide local excision with margins of 1 cm - trend is more conservative as radical vulvectomy doesn’t improve survival
• no survival advantage to lymph node dissection but RCT for intermediate thickness cutaneous melanomas elective node dissection had better survival
• Sential node biopsy has a 15% false negative rate - not standard practice

Question 12

Risk factors for treatment recurrence

Answer 12

• multifocal
• large lesions
• smokers
• immunocompromise
• positive surgical margins
• age
• raised solidarity lesions
• immunosuppression
• Previous tx to genital tract

Question 13

Prognosis for vulvar cancer

Answer 13

Prognosis
• 5 year survival with no lymph node involvement is in excess of 80%
• Less then 50% if lymph nodes re involved
• 10-15% if iliac or other pelvic nodes re involved
• Multifactorial analysis of risk factors for SCC prognosis showed nodal status and primary lesion diameter only variables that matter

Question 14

How to treat VIN

Answer 14

Treatment of VIN
• WLE - small lesion, lowest recurrence risk, 0.5-1cm margin, safe in pregnancy, histological dx
• Imiquimod cream 5% - 60% response rate - doesn’t cause scarring, topical, anaesthetic not required, use for large multifocal areas
• Local destruction - CO2 lazer, cryotherapy - less anatomical distorsion, can be used in pregnancy, single or multifocal confluent lesions, lacks assessment of occult invasion
• skinning vulvectomy
• Recurrence is 50% at 1 year
• No good evidence comparing txs

Question 15

Define Incisional biopsy

Answer 15

A biopsy taken with the intent of securing a diagnosis only. This should ideally contain the interface between normal and abnormal epithelium and be large enough for the pathologist to be able to adequately provide evidence of substage (in stage I cases).

Question 16

Define Excisional biopsy

Answer 16

A biopsy taken that includes all of the abnormal epithelium but does not provide a tumour-free zone of 1 cm (after fixation) on all dimensions. This would normally be performed in cases of vulval intraepithelial neoplasia (VIN) or when there is a low suspicion of invasive carcinoma and the operator wishes to limit the amount of cosmetic harm.

Question 17

Define radical excision

Answer 17

An excision performed with the intent of achieving clearance of at least 1 cm (after fixation) on all aspect of the tumour(s). Depending on the site and size of the tumour, this could vary from a radical local excision to a radical vulvectomy.

Question 18

DVIN - VIN differentiated type

Association
Who gets it
risk

Answer 18

•
o 5% premalignant conditons of the vulva
o Associated with LP / LS
o Older woman
o High risk of malignant transformation
o 60% SCC wth shorter time interval and higher recurrence rate

Question 19

• HSIL of the vulva - VIN usual type

Answer 19

o	HPV 16,18
o	Smoking, immunosuppression
o	Warty basaloid types
o	Younger woman, 35-49 
o	Multifocal, less potential for invasive malignancy
o	Vaccination reduces incidence
o	Majority or VIN 
o	Treatment is excision with 5mm border and 4 mm depth

Question 20

LSIL of the vulva -

Answer 20

flat condyloma, HPV effect

Question 21

VIN presentation

Answer 21

• Often delayed
• Generally 65 or older
• Lumps, burning, itch, irritation, pain, asymptomatic
• Lesions are red, white or pigmented, variable ,multifocal
• Enlarged groin nodes is a bad sign
• High index for suspicion and low index for biopsy
• Carefully examine for IN of the cx, vagina, perinanal area

Question 22

How to prevent vulval cancer

Answer 22

• Primary: HPV vaccination also reduces the risk of vulval cancer
• no specific screening
• Secondary: Woman with squamous intraepithelial lesions on the cx vagina or anus should have inspection of the vulva
• Tertiary prevention: treatment of predisposing and premalignant lesions

Question 23

Risk factors for VIN

Answer 23

Risks
•	Lichen sclerosis
•	High risk HPV (16)
•	Pagets disease
•	Melanoma insitu

Question 24

Lymphatic drainage of the vulva

Answer 24

• Primarily inguinofemoral region
• Secondarily to the external and internal iliacs
• This drainage is shared from with the inferior third of the vaginal tube and the most external portion of the anus (below the anal sphincter)
• Drainage can be unilateral or bilateral
• If the lesion is close to the clitoris it can be drained into the iliac region

Question 25

What does vulval care mean

Answer 25

* Soap substitute * Emollients * avoid soap, bubble bath, shower and bath additives, shampoo, hair conditioners and dyes * loose fitting clothing, avoid lycra, and nylon * wash after defecation / wipe front to back * Avoid condoms with spermicide * Avoid biological washing powders or fabric conditioners

Question 26

Examples of mild steroid moderate potent very potent

Answer 26

Mild Hydrocortisone 1% Moderate Clobetasone butyrate 0.05% Potent Betamethasone 0.1% Triamcinolone acetonide 0.1% Very potent Clobetasol propionate 0.05% Diflucortolone valerate 0.3%

Question 27

Complete vulva exam

Answer 27

Examination General Physical Examination • skin, mouth, back (LS spine) The vulva – magnified inspection with colposcope ◦ Anatomy / Skin – normal or abnormal ◦ Ask patient to localise the pain / lesion / site of itching ◦ Inspect for any lesions / erythema / ulcers / fissures / architectural changes / scars / atrophy – may require biopsy ◦ Vestibule – Q-tip test (note pain response and superficial muscle responses) ◦ Swabs – exclude candidiasis; STI (LVS, vulval swab for MCS and viral); biopsy Neuromuscular ◦ Assess pudendal nerve – palpate ischial spine; unilateral (pain on sitting and relieved by standing or lying; sensation of lump or fullness in vagina) ◦ Assess pelvic floor muscles for tenderness, tight bands, trigger points, bilateral symmetry Pelvic Organs ◦ Often coexisting endometriosis, IC / painful bladder syndrome, IBS ◦ Speculum / bimanual exam may be very traumatic

Question 28

What is lichen sclerosis

Answer 28

* Chronic inflammatory condition - aetiology unknown * Autoimmune - no specific antibody has been found * Genetic 10% has FHx F:M 10:1 * Associated with hypothyroidism and vitiligo, arthritis , pernicious anaemia, alopecia 30%+ FHx for autoimmune disease - recommend TSH + autoantibody tending * Related to squamous hyperplasia

Question 29

Who gets LS

Answer 29

* Peri + post menopausal woman 1:300 - 1:1000 mean age of onset 55 yo * can occur in children 1:900 girls 15% of all cases - does not become quiescent at puberty

Question 30

How does LS present Sc Describe typical appearance

Answer 30

* Pruritis, sore, itchy, dysparunia, urinary sx * characteristic appearance of white polygonal papules with coalesce and produce thickened white and crinkly skin often in a figure of 8 distribution - bilateral and symmetrical * Petechial haemorrhages and areas of atrophy * Can have areas of thickening / hyperkeratotic if there is concurrent squamous hyperplasia * The vulval architecture can be destroyed leading to loss of the labial minora, burying of the clitoris, narrowing of the introitus * Do not extend into the vagina or into the anus * Extragenital lesions - neck, buttocks, inner thigh, shoulder, wrist 6%

Question 31

Histopathology of LS

Answer 31

• Lichenoid inflammatory pattern; atrophic epidermis; hyperkeratosis; basal hydropic degeneration +/- pigmentary incontinence; lymphohistiocytic infiltrate in hyaline band with loss of elastic tissue in upper dermis; follicular plugging in hair bearing skin

Question 32

How to manage LS

Answer 32

* If dx uncertain then needs a biopsy * Vulval cares * potent or very potent steroids topically is effective - once relief achieved can use a less potent or use less often * Clobetasol propinoate 0.05% or betamethasone dipropionate 0.05% * mild recurrences can occur * Topical pimecrilinus and tacrolimus * Increased risk of SCC in 2-5% of woman so should have regular follow ups - we dont know who is at increased risk - annual once stable * Hormone treatment topically is not recommended * Surgery is not justified - occasionally division of adhesions is justified

Question 33

How does LP present

Answer 33

Presentation • More painful then itchy • Can extend into the vagina - they can have dysparunia and vaginal stenosis from scarring • Tends to occur in peri menopausal and menopausal women (40-60 yo). • Affects skin and mucous membrane – mouth, vulva, vagina, nails, scalp, oesophagus, nose, conjunctiva of the eye, ears, and bladder • Oral and genital LP onset together in up to 70% cases and oral starts first in 33%.

Question 34

Waht are the 2 forms of LP and how do they differ in presentation

Answer 34

• Classic form o purplish, flat topped, striated, polygonal papules o violaceous, well demarcated plaques with overlying lacy white lines which usually affect the labia majora and surrounding skin o Itching can be treated with moderate to potent topical steroid • Erosive form o Vulvual or introital soreness and dysparunia o adhesions if vaginal involvement o can occur on buccal mucosa o ‘glazed’ erythema or erosions symmetrically distributed at vaginal introitus - can go into vagina and onto cervix. White slightly raised edge to lesions. o Lacy white lines (Wickham’s striae) in surrounding skin. May have loss of anatomy.

Question 35

Aeitiology of LP

Answer 35

* Autoimmune disorder - mucocutaneous inflammatory disorder * disorder of altered T-cell mediated immunity to exogenous antigens targeting the basal keratinocytes of the epidermis; genetic factors * Rarely associated with vulval carcinomas * clinical diagnosis - biopsy shows non specific inflammation, dermal lymphocytic infiltrate with liquifaction of the basal epidermal layer, acanthosis and parakeratosis

Question 36

Histology of LP

Answer 36

• lichenoid reaction pattern; irregular saw-toothed acanthosis; increased granular layer; basal cell liquefaction; band-like dermal lymphocytic infiltrate

Question 37

Tx options LP

Answer 37

* Topical potent corticosteroids +/- intravaginal steroids * Oral prednisone * Topical tacrolimus / pimecrolimus * Oral/topical retinoids * Oral weekly methotrexate / azathioprine / cyclosporine / cyclophosphamide / mycophenolate * Vaginal dilators / Scarring and stenosis may require surgical treatment * Waxing and waning course * Long term follow-up required

Question 38

Vulval atophy - who gets it | Tx

Answer 38

* Postmenopausal, prepubertal and periods of prolonged lactation * Mucosa of the vagina is pale, thin, dry and loss of rugae * Prone to infection and can present with vaginal bleeding * Tx topical oestrogens * minimal effective dose for minimal time to prevent SEs

Question 39

Presentation of vulval dermatitis

Answer 39

* Hx atopic * Excema elsewhere * erythema and excoriations from intense pruritis * Lichenification common perinanally and on labia majora * Dry scaly lesions * Non symmetrical * Fissures * Vagina not affected

Question 40

Histology vulval dermatitis

Answer 40

• Histology: Spongiosis - oedema of epidermal layer of skin; variable acanthosis and superficial dermal lymphohistiocytic inflammatory infiltrate

Question 41

Management vulval dermatitis

Answer 41

* Vulvar cares * Eliminate contact / triggers * dx and tx any superinfection - candida, staph aureas, strep pyogenes * lifestyle modification - weight loss, treat incontinence * Soak and seal, cool packs, emollients * emollients or low potency steroids eg hydrocortisone 1%, sedation to stop nocturnal scratching / antihistamines * Oral steroids if needed

Question 42

Lichen Simplex Chronicus | Epidemiology

Answer 42

* 0.5% of caucasions * mid-late life adults * End stage itch scratch itch cycle * Part of the atopic dermatitis spectrum * 75% personal or family hx atopy * Triggered by psychological distress / change in loca lenvironment

Question 43

Signs and Sx | Lichen Simplex Chronicus

Answer 43

• Triggered by psychological distress / change in loca lenvironment Symptoms • chronic severe pruritis, worse at night; burning/soreness/dyspareunia associated with erosions or ulcers, disturbed sleep Signs • erythematous lichenified plaques, leathery feeling skin; erosions, ulcers, fissures; hyper-, hypo- or depigmented skin areas; broken hair

Question 44

Histology Lichen Simplex chonicus

Answer 44

Histology | • spongiosis and acanthosis; hyperkeratosis; parakeratosis; superficial perivascular infiltrate

Question 45

Management lichen simplex chronicus

Answer 45

Management • Vulvar cares • Eliminate contact / triggers • dx and tx any superinfection - candida, staph aureas, strep pyogenes • lifestyle modification - weight loss, treat incontinence • Soak and seal, cool packs, emollients • emollients or low potency steroids eg hydrocortisone 1%, sedation to stop nocturnal scratching / antihistamines • Oral steroids if needed

Question 46

Presentation vulvovaginal candida

Answer 46

* 20% of woman carry candida * Oestrogen dependant * Recurrent is 4 or mroe attaches of proven VVC in a year * Chronic is pt who is constantly symptomatic * Itchy, sore, dysparunia, burning, swelling, fissuring, pain, discharge * Sx recur once treatment ceased * Worse often premenstrually * Exacerbated by the OCP

Question 47

Tx vulvovaginal candida

Answer 47

Treatment • Daily oral antifungal for at least 1 month (Fluconazole 50-100mg/day or Itraconazole 100mg/day) • Nystatin 100 000U/5g vaginal cream, 1 applicator daily • Symptoms remit in 2 weeks to 6 months • Maintain remission with interval therapy once or twice weekly

Question 48

Genital warts presentation

Answer 48

``` Genital warts • HPV 6 and 11 • benign epithelial skin tumors • transmission perintal and through sexual contact • 18 month intubation period • 2.1/1000 per year before gardasil • Local irritation, pruritis, bleeding, discomfort, • Sponentous resolution 125 days in 30% • No therapy irradicates the infection ```

Question 49

Genital warts treatment

Answer 49

Podophyllotoxin 0.5% paint or 0.15% cream BD for 3 days then 4 days off and repeat for 4-6 weeks (paint for external skin, cream for perianal and introital) Self treatment Avoid in pregnancy Clearance 45-80%, recurrence variable ``` Imiquimod 5% Aldara Immune response modifier 3X / week for 16 weeks Wash off after 6-10 hours avoid in pregnancy local skin irritation can weaken condoms clearance 30-70% Recurrence 5-25% ``` Cryotherapy Liquid nitrogen Small lesions weekly for 3-4 months safe in pregnancy clearance 40-75% Recurrence 20-40% Excision Clearance 100% Recurrence 30% CO2 lazer / diathermy Large volume warts in difficult anatomical sites

Question 50

Provoked localised vulvodynia (Previously vulval vestibulitis)

Answer 50

* Mixed aeitiology - iatrogenic, genetic, dietary, related to pelvic floor spasm, * Localised to the introital area * Young woman 20-40 * No hx of abuse or psychosexual problems * May have been preceding infection eg candida but this is based on self reporting * Candida is no more common in woman with VVS then controls * Analogy with interstitual cystitis - the vestibule and the bladder/ urethral all form from the urogential sinus and there may be an increase in nerve density in these woman - no specific biopsy findings * Maybe be subtle reddish patches which are tender when touched with a cotton wool, * Woman develop vaginismus, loss of libido, loss of self esteem, * Hypertonic levator ani muscles

Question 51

Unprovoked generalised vulvodynia (previously called essential or dysaesthetic vulvodynia)

Answer 51

* Older woman - peri or post menopausal * Generalised burning and soreness in the absence of alterntive dianogis, not even introital tenderness, poorly localised, often perianal, can be provokes by touch but perisits after cessation of the stimulus often large area * Sx worse during the day, not changes by intercourse, difficult to treat * Normal vulval examination * Psychological co morbidity

Question 52

Vulvodynia management

Answer 52

``` Treatment - 4 Ps Patient educations and reassurance • Explain the condition • Reassure, give information • Specific treatments if indicated o Dermatological - steroids o Menopausal atrophy - HRT and oestrogen o Recurrent candida - fluconazole o VIN / SCC - treat OT • Vulva cares Pain modification • Topical o Lignocaine 5% - prior to sex o 2-6% gabapentin cream o 2% Amitriptyline cream • Avoid opiates • Amityiptyline - start low go slow o 10 mg nocte o titrate up o SE- dry mouth, sweating, dizziness, blurred vision, sedation, constipation, urinary retenion, cardiac arrhymias o up to 4 weeks until benefit • Gabapentin o Second line o 300 mg daily and titrate up - 1200mg tds o up to 8 weeks for full effect • Pregabalin o 50mg bd and gradually increase o max dose 300mg bd o SE- sedation, dizziness, headache, oedema, weight gain, tremor, nystagmis o Treat 3-6 months Physical therapy • General posture, gait, strength mobility • Abdo and hip assessment • pelvic floor muscle tension - often increased tone, trigger points, visceral spasm • Aim to restore function • Treat bladder and bowel dysfunction Psychological and psychosexual therapy • high levels of psychological distress and sexual dysfunction • Depression, anxiety and hx abuse increases risk of vulvar pain • Involve partner in therapy • minimise stress, relaxation, CBT, treat depression and anxiety ```

Question 53

Treatment of 1A

Answer 53

1A is 2cm or less and less then 1mm invasion into the stroma + no nodal involvement = radical wide local excision 2cm surgical margins

Question 54

Stage 1B or stage 2 cancers | how are they managed

Answer 54

Inguinofemoral lymphadenectomy - less then 1% of lesions that are less then 4cm and more then 2 cm from midline have contralateral nodal involvement so these cases can just have ipsilateral inguinal lymph node dissection

Question 55

What was the GROINSS - V study

Answer 55

European multicentre observations study about sentinal lymph node biopsy - and if negative omiting full lymphadenectomy ``` Criteria: Unifocal tumors confined to the vulva Tumors less than 4 cm in diameter Stromal invasion more than 1 mm Clinically negative groin nodes ``` 403 women were included and groin recurrences occurred in 2.3% of patients, with a median follow‐up of 35 months. Disease‐specific survival was 97% after 3 years, and surgical morbidity was substantially reduced

Question 56

After lymph node dissection who then gets radiation

Answer 56

Adjuvant RT improves survival Indicated for: Presence of extracapsular spread. Two or more positive groin nodes.

Question 57

How to manage advanced vulval cancer - spread beyond the vulva - bulky positive nodes

Answer 57

- confirm groin nodes with FNA or biopsy - CT / MET or PET assess the spread if non suspicious nodes then bilateral inguinofemoral lymphadenectomy and if + nodes then RT If OT inappropriate then chemoradiation If clinically positive nodes these should be removed + RT If ulcerated - radiation +/- chemo + Excision of the lesion if can do and leave sphincter function. Otherwise RT

Question 58

innervation of the vulva: The pudendal nerve has 3 branches What nerve root is it from

Answer 58

``` S2-4 is the pudendal nerve Sensory and motor nerve 3 branches Inferior rectal perineal dorsal nerve of the clitorus ``` Other nerves also cutaneous branch of ilioingunial genital branch of genitofemoral perineal branch of the posterior femoral cutanous nerve

Question 59

Blood supply of the vulva

Answer 59

Pudendal external and internal pudenal arteries branches into the dorsal artery of the clitoris (there is also a deep artery of the clitoris) Perineal inferior rectal artery

Question 60

Lymph drainage of the vulva?

Answer 60

distal third of the vagina | lateral to superficial and deep inguinofemoral nodes then to pelvic nodes